Mukherjee Devoshree, Ahmad Riaz, Nayeem Shahid
Section of Genetics, Department of Zoology, Faculty of Life Sciences, Aligarh Muslim University, Aligarh 202002, India.
Section of Genetics, Department of Zoology, Faculty of Life Sciences, Aligarh Muslim University, Aligarh 202002, India.
Int J Biol Macromol. 2022 Dec 1;222(Pt B):2936-2947. doi: 10.1016/j.ijbiomac.2022.10.069. Epub 2022 Oct 12.
Protein modulation is a process of changing protein structure which is either derived or deliberately induced. This leads to variation in protein activity during protein-protein interactions and can be utilized to understand disease mechanisms or to develop novel therapeutics. In this context, COX-2, iNOS and GST along with basic liver biochemistry were examined in experimentally injured rats and quercetin (QC) supplementation. Diethylnitrosamine (10 ml/kgbwt of 1%DEN) was used to generate liver injury in animals. Quercetin was administered at 60 mg/kgbwt daily in DEN-treated animals to investigate the effect. Hepatic AST/ALT/ALP/γGT, bilirubin, glycogen, LPO, CAT, SOD, GST, collagen levels, protein oxidation and nitrites were examined in all animals. Besides, histopathology and immunohistochemistry of COX-2 and iNOS was performed in tissue sections. Molecular docking of quercetin with human COX-2, iNOS and GST was performed by Autodock 4.2.6 software while drug likeliness and the properties of the ligand by SWISS-ADME and admetSAR and Molinspiration respectively. Our results demonstrate disturbed primary liver function concomitant with disconcert liver biochemistry and anatomy in DEN-treated animals (p < 0.05). Immunohistochemistry exhibited up-regulation of COX-2 and iNOS during liver injury. Molecular docking showed quercetin as acceptable drug as it passes Lipinski rule and shows binding with GST, iNOS, COX-2. In conclusion, COX-2, iNOS and GST appears to be the dynamic molecular targets of Quercetin action to restore tissue biochemistry and anatomy during experimental liver injury.
蛋白质调节是一个改变蛋白质结构的过程，这种改变可以是天然产生的，也可以是人为诱导的。这会导致蛋白质在相互作用过程中活性发生变化，可用于理解疾病机制或开发新的治疗方法。在此背景下，研究了实验性损伤大鼠和补充槲皮素（QC）后COX-2、诱导型一氧化氮合酶（iNOS）和谷胱甘肽S-转移酶（GST）以及基本肝脏生化指标的变化。用二乙基亚硝胺（1%的二乙基亚硝胺，10 ml/kg体重）诱导动物肝脏损伤。对接受二乙基亚硝胺处理的动物每天给予60 mg/kg体重的槲皮素，以研究其效果。检测了所有动物的肝脏天冬氨酸转氨酶/丙氨酸转氨酶/碱性磷酸酶/γ-谷氨酰转肽酶、胆红素、糖原、脂质过氧化、过氧化氢酶（CAT）、超氧化物歧化酶（SOD）、GST、胶原蛋白水平、蛋白质氧化和亚硝酸盐含量。此外，还对组织切片进行了COX-2和iNOS的组织病理学和免疫组织化学检测。使用Autodock 4.2.6软件对槲皮素与人COX-2、iNOS和GST进行分子对接，同时分别通过SWISS-ADME、admetSAR和Molinspiration分析配体的药物相似性和性质。我们的结果表明，在接受二乙基亚硝胺处理的动物中，肝脏的主要功能受到干扰，同时肝脏生化指标和解剖结构也出现紊乱（p < 0.05）。免疫组织化学显示肝脏损伤期间COX-2和iNOS上调。分子对接表明，槲皮素符合Lipinski规则，可作为一种可接受的药物，并且显示出与GST、iNOS、COX-2结合。总之，COX-2、iNOS和GST似乎是槲皮素在实验性肝损伤期间恢复组织生化和解剖结构作用的动态分子靶点。
